Document M4OBqzg865LyEQ42Y5RdvQg2M
FILE NAME: Talc (TALC)
DATE: 1997
DOC#: TALC026
DOCUMENT DESCRIPTION: Journal Article - Perineal Powder Exposure and the Risk of Ovarian Cancer
t '
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Jl(suppl 6):
American Journal of Epidemiology
Copyright 1997 by The Johns Hopkins University School of Hygiene and Public Health All rights reserved
Vol. 145, No. 5 Printed in U.S.A.
of automo ers in New
ty of filling h 1994:20:
Perineal Powder Exposure and the Risk of Ovarian Cancer
-xposure t(> ocytic leu
te myeloid nded case -6. -'ukemia in set. Eur J
gasoline in ill, Thorpe oxicologs, Princeton 72. A chronic 1 Am Coll
Linda S. Cook,1 Mary L. Kamb,1'2 and Noel S. Weiss 1,2
This case-control study evaluated the risk of epithelial ovarian cancer associated with genital exposure to Wa^hin ?rmS h powde!;apP|lcatlon- Cases included all women aged 2 0 -79 years in three counties of western Washington who were diagnosed with borderline or invasive ovarian cancer from 1986 throuqh 1988' 64 3% of eligible cases were interviewed. A sample of similarly aged women who lived in these counties, identified
y random digit dialing, served as controls. The overall response among control women was 68 0% nformation on powder application and other potential risk factors was ascertained during the in-person interview. Overall, ovarian cancer cases (n = 313) were more likely than controls (n = 422) to ever have used an^nteh i a9e?hdJHSteid relatT nSk (RR) = 1'5 ' 95% confidence interval <CI) 1-1-2.0). After adjustment for age and other methods of genital powder application (none vs. any), an elevated relative risk of ovarian cancer was
im-related : 1985;27:
ell cancer id J Work
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asoline: a : 111-14. -"rnational 1995:61:
IntemuJ Cancer
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rol study s. Am J
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pational ion: Her
-tigation ons and 971;14:
mserva-tasoline 4/87). ige me ns from 94.
, 1997
so av iRRyI i q i ! v m h
P8rineal dUSting (RR = 1 6' 95% Cl 1-1- 2-3>or use of 9enital deodorant
spray (HR 1.9, 95 /o Cl 1.1-3.1). These results offer support for the hypothesis, raised by prior epidemiologic
studies, that powder exposure from perineal dusting contributes to the development of ovarian cancer and
they suggest that use of genital deodorant sprays may do so as well. Limitations of the present study include
the fairly low proportion of eligible women who participated and the potential differential recall of powder usage. Am J Epidemiol 1997;145:459-65.
ovarian neoplasms; powders; talc
Studies documenting the migration of carbon parti cles and radioactive particulate agents from the vagina to the ovaries (1, 2), as well as those that have identiiied talc-like particles more frequently in ovarian tumors than in normal human ovarian tissue (3), have raised concern that genital powder exposure may in crease a woman's risk of developing ovarian cancer. While the results of several epidemiologic studies have suggested elevated risks for ovarian cancer among women with genital powder exposures (4-11), results have been inconsistent for particular methods of powder application (12). In this population-based case-control study, information on the method, dura tion, and frequency of powder application was col lected to evaluate the impact of genital powder expo sures on the risk of epithelial ovarian cancer.
MATERIALS AND METHODS
Women with invasive or borderline epithelial ovar ian cancer were identified from records of the popu-
Received for publication May 20, 1996, and accepted for publi cation October 22, 1996.
Abbreviations: Cl, confidence interval; RR, relative risk. 1 Fred Hutchinson Cancer Research Center, Seattle, WA. 2 Department of Epidemiology, University of Washington Seat tle, WA. Reprint requests to Dr. Linda S. Cook, MP-381, Fred Hutchinson Cancer Research Center, 1124 Columbia Street, Seattle, WA 98104.
lation-based Cancer Surveillance System of western Washington. Eligible case subjects included white women diagnosed between January 1. 1986, and De cember 31, 1988, who resided in three counties of western Washington (King, Pierce, and Snohomish counties) and were 20-79 years of age at diagnosis. After obtaining permission from their personal physi cians to contact the women and obtaining written, informed consent, we successfully interviewed 329 (64.3 percent) of the 512 eligible case subjects. The remaining 183 women were not interviewed because of death prior to study contact (n = 104, 20.3 percent), physician or subject refusal (n = 73, 14.3 percent), and lack of success in locating the women ( = 6, 1.2 percent). Seven women whose self-reported race/ ethnicity was other than white and nine women with unknown genital powder use were also excluded. Thus, a total of 313 white women diagnosed with borderline (n = 79) or invasive (n = 234) epithelial ovarian tumors were available for analysis.
Women identified as control subjects for this study were part of a larger control pool selected by random digit dialing (13) for several studies of cancer in women. Of the total 10,109 calls made by random digit dialing, 5,853 (57.9 percent) were to nonresiden tial phone numbers, 3,830 (37.9 percent) were to res idential phone numbers, and 426 (4.2 percent) were to
459
460 Cook et al.
numbers of unknown residential status; 3,604 (94.1 method of powder application, the risk for ovarian 3 3 percent) of the 3,830 calls to residential households cancer among women who reported any use of the four
were screened for eligible women who were age methods of powder application was assessed while
matched, in 5-year age groups, to the combined female adjusting for the other methods of powder application Oo ^i cancer case group. Of the 721 women identified who (table 3). Similarly, ovarian cancer risk by exclusive CO : were eligible, 521 (72.3 percent) were successfully and nonexclusive use of the type(s) of powder used for
interviewed after written, informed consent was ob perineal dusting, diaphragm storage, or on sanitary
J2 J y T 3 iv
tained. The overall response (random digit dialing
napkins was assessed (table 4). To assess the impact of
0)
(J
screening response multiplied by the interview re genital powder exposure on the risk of specific histo
0) w
o - sponse) was 68.0 percent. Women who reported race/ logic categories of ovarian tumors (table 5), we
Q_
<1) -
ethnicity other than white (n = 28), age greater than
grouped borderline and invasive ovarian tumors ac
X>3, 79 (n = 5), a history of bilateral oophorectomy cording to the following International Classification
03 '
E /
(n = 58), uncertainty concerning a history of bilateral
o f Diseases fo r Oncology histologic codes (15): serous
o i
Ca: -ri,
oophorectomy (n = 4), and unknown genital powder
tumors (codes 8441, 8442, 8460, 8461, and 8462):
>>* use (n = 4) were excluded, resulting in a total of 422 mucinous tumors (codes 8470, 8472, 8473, 8480, and
03 s CL ^
white control women for analysis.
8481); endometrioid tumors (codes 8380, 8381, and
a ;
Information regarding genital powder exposures 8560); and other tumors that included clear cell (code
03
was collected by structured, in-person interviews. 8310), undifferentiated (code 8020), and unclassified/
.O>"*s"t Women were queried about storing diaphragms in other (codes 8010, 8050, 8140, 8240, 8260, 8440.
03 5 o 5
powder, dusting perineal areas with powder after bath
8450, and 9000). All relative risk estimates were ad
TD ing, powdering sanitary napkins, and using genital justed for age. Further adjustment for education, in
deodorant sprays (which may contain aerosolized come, marital status, body mass index (weight (kg)/ O ; powder). Those who answered affirmatively were height (m)2), oral contraceptive use, or parity did not
questioned further about the duration and frequency of alter the estimated relative risks. Information on lac
powder application and about the types of powder tation was not available. Separate analyses for women
applied. Powders were grouped into five categories: diagnosed with invasive ovarian cancer and for those
cornstarch, talcum powder, baby powder, deodorant diagnosed with borderline ovarian cancer produced
powder, and scented body/bath powder. Information results very similar to those presented in tables 2-5. -C * on demographic characteristics, reproductive history,
medical and screening histories, smoking history, an b * thropometry, and birth control methods was also pro RESULTS
vided by the women. A calendar was used to record major life events and enhance recall of past exposures. Relevant study information was recorded only for exposures that occurred prior to the diagnosis date of cancer among the cases or the analogous reference date among controls.
Logistic regression (EGRET version 26.6; Statistics
Selected characteristics of ovarian cancer cases and controls are presented in table 1. Less education, a lower household income, and a higher body mass index were more common among women with ovarian cancer than among control women, but oral contracep tive use and having had a full-term birth were less common.
and Epidemiology Research Corporation, Seattle,
Genital powder application was more common
Washington) was used to determine odds ratios as estimates of the relative risk for ovarian cancer asso
among cases (50.8 percent) than controls (39.3 per cent) (table 2). There was an overall 50 percent ele
ciated with genital powder application and 95 percent vation in the risk for ovarian cancer associated with
o *E
confidence intervals (14). For all the relative risk es the use of one or more of the four possible methods of
b
timates reported in the present analysis, women who genital powder application (95 percent Cl 1.1--2.0).
re reported any method, type, or frequency of genital Among women who exclusively used a single method
powder application were compared with women who of powder application, ovarian cancer risk was most
stated that they had never applied genital powder in strongly elevated among those who dusted perineal
any manner (154 ovarian cancer cases and 256 con areas with powder after bathing (RR = 1.8, 95 percent
trols). Trends were evaluated using the likelihood ratio statistic (14).
Cl 1.2-2.9). We further examined ovarian cancer risk among
First, the relative risk for ovarian cancer among women who reported application of genital powders
women who reported exclusive use of one of the four using each of the four methods, although not neces
methods of powder application was assessed (table 2). sarily exclusive use of any method (table 3). Perineal
Then, because many women used more than one dusting was associated with an increased risk of ovar-
Am J Epidemiol Vol. 145, No. 5, 1997
ian can. though with inc tributioi tubal lr relative shown), untary g powder^ cancer 1 1976 or 1977 or in 1976
Am J Ep,
Powder and Ovarian Cancer 461
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varian ie four while cation -lusive >ed for tnitarv oact of histoi), we >rs accation serous 8462j; '0, and 1, and ' (code -sifted/ 8440, ?re ad on, in t (kg)/ lid not >n lacvomen ;those tduced - 2-5,
es and tion, a
mass tvarian tracepre less
immon .3 pernt eled with lods of 1- 2.0 ). nethod s most erineal oercent
among owders neces"erineal if ovar-
5, 1997
TABLE 1. Characteristics of epithelial ovarian cancer cases and controls: King, Pierce, and Snohomish counties, Washington State, 1986-1988
Characteristic
Age (years) 20-34 35-44 45-54 55-64 65-79
Education (years) <8 9-12 13-16 >16 Unknown
Annual household Income ($) <15,000 15,000-30,000 >30,000-45,000 >45,000 Unknown/refused
Marital status Single Married Separated/divorced/widowed
Body mass index (kg/m2) <21 21-22 23-24 >25
Oral contraceptive use Never or <12 months >12 months but <5 years >5 years
Total pregnancies 0 1 >2 Unknown
Total full-term births 0 1 >2 Unknown
Cases (n = 313)
No.
%
34
10.9
50
16.0
60
19.2
88
28.1
81
25.9
15
4.8
124
39.6
146
46.6
27
8.6
1
0.3
90
28.8
91
29.1
60
19.2
63
20.1
9
2.9
32
10.2
186
59.4
95
30.4
56
17.9
89
28.4
73
23.3
95
30.4
224
71.6
50
16.0
39
12.5
57
18.2
42
13.4
214
68.4
0
79
25.2
46
14.7
188
60.1
0
Controls
(n = 422)
No.
%
84
19.9
136
32.2
65
15.4
63
14.9
74
17.5
14
3.3
144
34.1
219
51.9
45
10.7
0
83
19.7
153
36.3
81
19.2
96
22.7
9
2.1
33
7.8
292
69.2
97
23.0
97
23.0
145
34.4
75
17.8
105
24.9
221
52.4
93
22.0
108
25.6
56
13.3
56
13.3
309
73.2
1
0.2
83
19.7
69
16.4
269
63.7
1
0.2
ian cancer (RR = 1.6, 95 percent Cl 1.1-2.3), al though there was no clear pattern of increasing risk with increasing duration of use. When the small con tribution of perineal dusting after a hysterectomy or tubal ligation was excluded from the analysis, our relative risk estimates were nearly unchanged (data not shown). In 1976, the cosmetic industry proposed vol untary guidelines to limit contamination of consumer powders (16), and we attempted to evaluate ovarian cancer risk associated with any perineal dusting in 1976 or before and with exclusive perineal dusting in 1977 or thereafter. Women with any perineal dusting in 1976 or before had an elevated risk (RR = 1.8, 95
Am J Epidemiol Voi. 145, No. 5, 1997
percent Cl 1.1-2.9), but we were unable to evaluate exclusive perineal dusting in 1977 and thereafter since only four cases and 10 controls had this exposure. The use of genital deodorant sprays was also associated with an elevated ovarian cancer risk (RR = 1.9, 95 percent Cl 1.1-3.1), with the strongest elevation in risk among the small number of women {n -- 15) who used these sprays for more than 1 year (RR = 2.7, 95 percent Cl 1.1-6.6). Storing a diaphragm in powder or powdering sanitary napkins was not related to the risk of developing an ovarian tumor (RR := 1.0, 95 percent Cl 0.6-1.6, and RR = 0.9, 95 percent Cl 0.5-1.5, respectively).
462 Cook et al.
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2' Re,a.tive ,risk of eP'thelial ovarian cancer associated with any genital powder use and bv
exclusive use of various methods of powder application* Kina Pierce and Snnhnmici,
^
Washington State, 1986-1988
9'
' and Snohom,sh counties,
Powder application
Lifetime genital powder application None Any
Ovarian
cancer cases
(n = 313)
Controls
(n = 422)
RR*
No.
%
No.
%
154
49.2
256
60.7
1.0
159
50.8
166
39.3
1.5
Exclusive use of Perineal dusting only Diaphragm storage in powder only Powder on sanitary napkins only Genital deodorant spray only
55
17.6
22
7.0
12
3.8
18
5.8
48
11.4
1.8
35
8.3
0.8
10
2.4
1.5
28
6.6
1.5
* RR. relative risk, adjusted for age; Cl, confidence interval.
95% Cl*
Referent 1.1-2.0
1.2-2.9 0.4-1.4 0.6-3.6 0.8-3.0
No specific type of powder used for perineal dust ing, diaphragm storage, or on sanitary napkins was strongly related to ovarian cancer risk, although there was a suggestion of an elevated risk associated with any use of talcum powder and bath/body powders (RR = 1.6, 95 percent Cl 0.9-2.8, and RR = 1.5, 95 percent Cl 0.9-2.4, respectively) (table 4). When spe cific histologic categories of ovarian tumors were ex amined, any genital powder application was associated with an elevated risk for serous tumors (RR = 1.7, 95 percent Cl 1.1--2.5) and the nonspecific category of other tumors (RR = 1.8, 95 percent Cl 1.1-2.8), whereas no elevation in risk was noted for the small number of women with mucinous tumors (RR = 0.7, 95 percent Cl 0.4-1.4) or endometrioid tumors (RR = 1.2, 95 percent Cl 0.6-2.3) (table 5).
DISCUSSION
There are several issues that should be considered in the interpretation of our results. A sizable number of women eligible for our study did not participate, par ticularly among those with ovarian cancer. Many women with cancer died before they could be ap proached about participation in this study, and others were too ill to participate. If substantial differences in powder use existed between participating and nonpar ticipating women, our study results may over- or un derestimate the true risks for ovarian cancer. It is also possible that the completeness of the reporting of powder use differed between cases and controls, bias ing our relative risk estimates to some degree. '
Additionally, it is not clear how well ascertainment of perineal powder application correctly estimates ac tual exposure to particles in powder that may influence ovarian cancer risk. Different consumer brands of powder that women used, or even different lots of the same brand, may have varied substantially in the con
tent of talc, asbestiform minerals, or structurally sim ilar compounds. Powder content has also varied over time, presumably with fewer asbestiform minerals present in more recently manufactured products (17 19).
Our results suggest that a history of perineal dusting or use of genital deodorant sprays has a modest influ ence on the development of epithelial ovarian tumors, whereas storing a diaphragm in powder or powdering sanitary napkins does not. Direct comparisons of our results with those of the other nine published studies (and among these studies) are somewhat limited be cause of differences in the definitions, groupings, and analysis of genital powder use. Nonetheless, there is some consistency in results among studies. Seven studies including the present one (4, 6, 8-11) reported elevated relative risks for ovarian cancer, ranging from 1.3 to 3.9, among women with powder exposure by "dusting of the perineum." Of the three remaining studies that evaluated the more general exposure of "talc use in genital/perineal area" (which may or may not include perineal, sanitary napkin, diaphragm, or undergarment applications), two observed a modest elevation in ovarian cancer risk (5, 7), whereas one did not (20).
Most studies including the present one have found little, if any, excess risk for ovarian cancer among women who stored their diaphragms in powder (4-& 10), only one study has reported a suggestion of an elevation in risk (11). In the present study, control women more frequently reported washing their dia phragms prior to use than did ovarian cancer cases, but ovarian cancer risk was not substantially elevated for the small number of women who did not wash their diaphragms prior to use. The relation between pow dering sanitary napkins and ovarian cancer risk is less clear; three studies including the present study found
Am J Epidemiol Vol. 145, No. 5. 1997
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Powder and Ovarian Cancer 463
TABLE 3. Relative risk of epithelial ovarian cancer associated with genital powder use by methods of powder application: King, Pierce, and Snohomish counties, Washington State, 1986-1988*
None
Lifetime genital
powder application
Ovarian
cancer cases (n = 313)
No.
%
Controls
(n = 422)
RRf
No.
%
154
49.2
256
60.7
1.0
95% Cl* Referent
Any perineal dusting Cumulative lifetime days <2,000 2,001-5,000 5,001-10,000 >10,000 Unknown
95
30.4
20
6.4
24
7.7
21
6.7
28
8.9
2
0.6
87
20.6
1.6
22
5.2
1.8
26
6.2
1.6
22
5.2
1.2
17
4.0
1.8
0
1.1-2.3
0.9-3.5 0.9-2.9 0.6-2.4 0.9-3.4
Diaphragm storage in powder Cumulative lifetime months <60 >60 Unknown Usually washed before use No Yes Unknown
46
14.7
24
7.7
15
4.8
7
2.2
19
6.1
20
6.4
7
2.2
51
12.1
1.0
26
6.2
1.1
20
4.7
0.8
5
1.2
14
3.3
1.4
31
7.3
0.7
6
1.4
0.6-1.6 0.6-1.9 0.4-1.7
0.7-3.0 0.4-1.4
Any powder on sanitary napkins
38
12.1
40
Cumulative lifetime months
<120
25
8.0
21
>120
12
3.8
19
Unknown
1
0.3
0
Lifetime applications
<1,000
23
7.3
19
>1,000
14
4.5
21
Unknown
1
0.3
0
9.5
0.9
5.0
1.3
4.5
0.5
4.5
1.3
5.0
0.6
0.5-1.5 0.7-2.4 0.2-1.1
0.7-2.5 0.3-1.2
Any genital deodorant spray Cumulative lifetime months <12 >12 Unknown Lifetime applications <500 >500 Unknown
40
12.8
40
9.5
1.9
1.1-3.1
24
7.7
31
7.4
1.5
0.9-2.8
15
4.8
9
2.1
2.7*
1.1-6.6
1
0.3
0
29
9.3
34
8.1
1.7
1.0-2.9
10
3.2
6
1.4
2.6*
0.9-7.6
1
0.3
0
* Numbers do not add up to total cases and controls because women may have used a variety of methods for powder application.
t RR, relative risk, adjusted for age and for the other methods of genital powder application (none, any); Cl,
confidence interval.
' '
* p value for trend < 0.05.
no association (6, 10), whereas three other studies reported moderate elevations in risk (4, 8, 11).
Only two other studies have evaluated particular types of powder; one reported an excess risk of bor derline ovarian tumors among women who used de odorant powders (8), and another study reported an excess risk of ovarian cancer among women who used baby powders (10). A strong relation between the types of powder used and ovarian cancer risk was not found in the present study, although there was a sug gestion of an elevated risk with any use of talcum
Am J Epidemiol Vol. 145, No. 5, 1997
powder and bath/body powders among women using these powders for perineal dusting, diaphragm storage, or on sanitary napkins.
The present study is the first to evaluate the associ ation between genital deodorant spray use and ovarian cancer risk; these preliminary results require confir mation in other studies. It is difficult to postulate that an increased risk for ovarian cancer may specifically be due to powder and associated constituents when some of the deodorant sprays do not contain aerosol ized powder. It is possible that it is not powder per se
hat may r is un ii fibrous hydrous all bod) cifically lfibrous. e across the skin, is parti ' can be is relainclude in open moconi-
5, 1997
Powder and Ovarian Cancer 465
osis (talcosis) in individuals with long-term exposure to talc dust (19). Occupational exposure to talc does not appear to increase the risk for pulmonary malig nancies (19). Most animal studies confirm this, with lung tumors developing only in rats exposed to doses of talc dust high enough to cause chronic obstructive and restrictive lung toxicity (19). Excess ovarian tu mors have not been reported in rats and mice with long-term exposure to aerosol talc (23). In contrast, occupational exposure to asbestos fibers has been shown to cause lung tumors (24) and has been asso ciated with the development of ovarian tumors (25). Thus, while there is little biologic or experimental evidence to support a role for talc per se in the devel opment of ovarian malignancies, the potential biologic effects of consumer powders (with their variable con stituents) on the human ovary have not been well studied. The prevalence of genital powder exposure re ported among control women in this and other studies conducted in the United States ranges from 28 percent to 51 percent (4-6, 8, 10). Given such a common prac tice, even the modest elevation in ovarian cancer risk associated with genital powder application suggested b>' most of the epidemiologic studies could have a notable impact on the incidence of ovarian cancer in the United States. We recommend that cohort studies address this question; these studies could eliminate concerns regarding the potential differences in the report ing of genital powder exposures between cases and con trols. We also believe that further characterization of the constituents of powder products that may influence ovar ian cancer risk and the investigation of their possible biologic mechanisms of carcinogenesis are warranted.
ACKNOWLEDGMENTS
This research was supported by grant R35 CA39779 from the National Cancer Institute and by the Cancer Surveil lance System o f the Fred Hutchinson Cancer Research Center, which is funded by contract no. N 01-C N -05230 from the Surveillance, Epidemiology, and End Results (SEER) Program o f the National Cancer Institute with ad ditional support from the Fred Hutchinson Cancer Research Center.
The authors thank Kay Byron and Judy Kuskin for their programming assistance, Diana Farrow for assistance with data collection, and Robert C. Lee for his review o f the manuscript and insightful comments.
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